Neuroprotective Effects of N-methyl-D-aspartate Receptor Antagonist on Aspartate Induced Neurotoxicity in the Spinal Cord in vivo

Yasunori Cho, Toshihiko Ueda, Atsuo Mori, Hideyuki Shimizu, Ryohei Yozu

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Objective: Much evidence has been gathered to show that neurotoxicity of excitatory amino acids is mainly activated through an N-methyl-D-aspartate (NMDA) receptor cascade. We evaluated the protective effects of NMDA receptor antagonists, MK-801 and CGS19755 on spinal cord neurons using the NMDA receptor mediated neurotoxicity model in vivo. Methods: New Zealand white rabbits underwent an infrarenal aortic isolation. Group A animals (n = 7) received segmental aspartate (50 mM) infusion for 10 minutes. Group B animals (n = 6) were pretreated with MK-801 (6mg/kg), a noncompetitive NMDA receptor antagonist, that was administrated intravenously for 3 hours beginning 1 hour before the segmental infusion of aspartate (50 mM) of 10 minutes. Group C animals (n = 6) received pretreatment with CGS19755 (30mg/kg), a competitive NMDA receptor antagonist, that was administrated in the same fashion as group B, followed by the segmental infusion of aspartate (50 mM). Neurologic status was scored at 12, 24, and 48 hours after operation using the Tarlov score. All the animals were sacrificed for histologic assessment at 48 hours. Results: Group A animals exhibited paraplegia or paraparesis with marked neuronal necrosis. Group B and C animals showed significantly better neurologic function compared with group A (p = 0.0013, A vs. B) (p = 0.0011, A vs. C). Pathohistological change was not observed in group B and C animals. Conclusions: NMDA receptor antagonists can have protective effects on spinal cord neurons against aspartate induced neurotoxicity. This model may be useful in assaying protective agents in the spinal cord against neuronal injury mediated by NMDA receptors in vivo.

Original languageEnglish
Pages (from-to)500-505
Number of pages6
JournalJapanese Journal of Thoracic and Cardiovascular Surgery
Volume51
Issue number10
Publication statusPublished - 2003 Oct

Fingerprint

Neuroprotective Agents
N-Methyl-D-Aspartate Receptors
Aspartic Acid
Spinal Cord
Dizocilpine Maleate
Nervous System
Paraparesis
Neurons
Protective Agents
Excitatory Amino Acids
Paraplegia
Necrosis
Rabbits
Wounds and Injuries

Keywords

  • Aspartate neurotoxicity
  • CGS19755
  • MK-801
  • N-methyl-D-aspartate receptor
  • Paraplegia

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Neuroprotective Effects of N-methyl-D-aspartate Receptor Antagonist on Aspartate Induced Neurotoxicity in the Spinal Cord in vivo. / Cho, Yasunori; Ueda, Toshihiko; Mori, Atsuo; Shimizu, Hideyuki; Yozu, Ryohei.

In: Japanese Journal of Thoracic and Cardiovascular Surgery, Vol. 51, No. 10, 10.2003, p. 500-505.

Research output: Contribution to journalArticle

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abstract = "Objective: Much evidence has been gathered to show that neurotoxicity of excitatory amino acids is mainly activated through an N-methyl-D-aspartate (NMDA) receptor cascade. We evaluated the protective effects of NMDA receptor antagonists, MK-801 and CGS19755 on spinal cord neurons using the NMDA receptor mediated neurotoxicity model in vivo. Methods: New Zealand white rabbits underwent an infrarenal aortic isolation. Group A animals (n = 7) received segmental aspartate (50 mM) infusion for 10 minutes. Group B animals (n = 6) were pretreated with MK-801 (6mg/kg), a noncompetitive NMDA receptor antagonist, that was administrated intravenously for 3 hours beginning 1 hour before the segmental infusion of aspartate (50 mM) of 10 minutes. Group C animals (n = 6) received pretreatment with CGS19755 (30mg/kg), a competitive NMDA receptor antagonist, that was administrated in the same fashion as group B, followed by the segmental infusion of aspartate (50 mM). Neurologic status was scored at 12, 24, and 48 hours after operation using the Tarlov score. All the animals were sacrificed for histologic assessment at 48 hours. Results: Group A animals exhibited paraplegia or paraparesis with marked neuronal necrosis. Group B and C animals showed significantly better neurologic function compared with group A (p = 0.0013, A vs. B) (p = 0.0011, A vs. C). Pathohistological change was not observed in group B and C animals. Conclusions: NMDA receptor antagonists can have protective effects on spinal cord neurons against aspartate induced neurotoxicity. This model may be useful in assaying protective agents in the spinal cord against neuronal injury mediated by NMDA receptors in vivo.",
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